Fall Research Expo 2024

Lebercilin Mutations Associated With Photoreceptor Protein Loss

Leber congenital amaurosis (LCA) is a group of inherited retinal diseases characterized by severe impaired vision or blindness at birth. LCA is caused by the degeneration and dysfunction of photoreceptors. It is an autosomal recessive disease, meaning a child must inherit two LCA mutated gene copies, one from each parent. Symptoms of LCA in children include visual impairment, constant rubbing of eyes, nystagmus, and poorly reactive pupils. LCA is monogenic and mutations in at least 27 genes are known to be responsible, including LCA5, which is the main focus of this poster. LCA5 is one of the genes that causes Leber Congenital Amaurosis, and it does so by affecting intraflagellar transport (IFT), which is the bidirectional movement of proteins from the inner segment of photoreceptors to the outer segment of photoreceptors, and vice versa. LCA5 codes for the protein Lebercilin, which is a protein found in the connecting cilium (a region that connects photoreceptor inner and outer segments) that assists in IFT. The lack of lebercilin disrupts IFT, which can prevent essential proteins for vision from functioning the way they should. Two such proteins are Prom1 and CtBP2. Prom1 is a protein found in the OS of photoreceptors, and it is thought to play a role in the structural organization of the OS, as well as OS disc morphogenesis. CtBP2 is a protein found in the plexiform layers of the retina, and is a major component of synaptic ribbons; it is thought to play a role in tethering synaptic vessels to the ribbon, which allows for the release of neurotransmitters and the transmission of sensory information. Both proteins play an important role in maintaining photoreceptor structure and function, and my objective this summer was to determine how LCA5 -/- affected the levels of Prom1 and CtBP2 in the retina. Through immunohistochemistry I found that the areas of the Outer Nuclear Layer (ONL) and Inner Nuclear Layer (INL) of photoreceptors decreased in LCA5 -/- mice over time. I also found that Prom1 levels decrease in LCA5 -/- mice relative to their wild type counterparts, which can be seen in figure 4, and that CtBP2 levels decrease in LCA5 -/- mice relative to their wild type counterparts in figure five. Figure six provides qPCR data showing again that Prom1 and CtBP2 levels decrease in LCA5 -/- mice over time relative to their wild type counterparts. Further research is needed to determine whether or not the loss of Prom1 and CtBP2 directly results from LCA5 -/-, or some other factor entirely.

PRESENTED BY
PURM - Penn Undergraduate Research Mentoring Program
College of Arts & Sciences 2026
Advised By
Dr. Katherine Uyhazi
Assistant Professor of Ophthalmology
PRESENTED BY
PURM - Penn Undergraduate Research Mentoring Program
College of Arts & Sciences 2026
Advised By
Dr. Katherine Uyhazi
Assistant Professor of Ophthalmology

Comments